Factors associated with unknown primary status in head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck cancer of unknown primary (CUP) poses significant therapeutic challenges. We compare CUP and oropharyngeal primary (OP) cases to identify factors associated with tumor detection. METHODS: The 2004-2019 National Cancer Database was queried to identify CUP and OP cases based on clinical and pathologic TNM staging. Clinical and demographic characteristics were compared by primary detection and HPV status with descriptive statistics. Multivariable logistic regression models to characterize OP detection were constructed. Among HPV-positive and negative patients, respectively, OP and CUP patients were matched by clinical nodal disease. Cox proportional-hazards models were constructed using matched cohorts to characterize survival. RESULTS: 81,053 CUP and OP cases were identified; 64.3 % were HPV-positive. OP detection increased over time in HPV-positive and negative disease. HPV-positive status had higher odds of OP detection (odds ratio (OR) = 1.77, p < 0.001), while females (OR = 0.95, p = 0.008), and black (OR = 0.82, p < 0.001) and Asian (OR = 0.7, p < 0.001) patients had lower odds compared to males and whites, respectively. In HPV-positive and negative disease, OP patients had higher 2 and 5-year survival rates than CUP (p < 0.001). Primary detection status conferred lower death risk in HPV-positive (hazard ratio (HR) = 0.85, p < 0.001) and negative disease (HR = 0.87, p < 0.001) when controlling for age, sex, race, comorbidities, insurance, treatment facility, and income. CONCLUSION: In the largest cohort of CUP to date, we report a survival benefit in primary tumor detection regardless of HPV status. Groups with higher persistent CUP rates, including non-white, female, HPV-negative, and low income patients, may benefit from increased diagnostic workup to improve detection and treatment.

Reasons for COVID-19 Vaccine Hesitancy Among Patients Listed for Solid Organ Transplants.

BACKGROUND: Patients listed for solid organ transplants (LSOTP) are at high risk for severe COVID-19 outcomes. Despite national guidelines recommending COVID-19 vaccination for LSOTP, vaccine hesitancy and underuse are reported in this population; however, reasons for this finding have not been examined thoroughly. METHODS: This single-center retrospective survey analysis aimed to characterize reasons for COVID-19 vaccine hesitancy among 110 heart, liver, and kidney patients LSOTP who had not received all the recommended vaccine doses at the time of the study. Survey questions also investigated experiences with influenza vaccination. RESULTS: Fifty-four patients (49.1%) responded to the telephone survey. The most common reasons for vaccine hesitancy were perceived lack of research in vaccine development (31%), fear of vaccine-related side effects (22%), and belief that the vaccine was unnecessary (20%). Of the respondents, 35% reported changing their vaccine perception after being listed for a transplant, most commonly attributing this to a perception that the COVID-19 vaccine is not safe for transplant recipients (32%). Gender differences in hesitancy reasons were observed, with males more likely to delay vaccination until after transplantation, although this difference was not significant (P = .07). Despite these findings, 54% of all respondents reported receiving annual influenza vaccines consistently. CONCLUSION: Despite their risk, patients LSOTP show significant hesitancy toward COVID-19 vaccines owing to perceived safety and necessity issues. The results of this study can inform targeted educational efforts to address and rectify misconceptions and concerns about COVID-19 vaccination among patients LSOTP. Future studies focused on larger, more diverse cohorts are needed to expand our understanding of and address vaccination hesitancy among this vulnerable patient population.

Vascular effects of apelin in vivo in man.

OBJECTIVES: This study was designed to establish the direct vascular effects of apelin in vivo in man. BACKGROUND: Apelin is the endogenous ligand for the previously orphaned G-protein-coupled receptor, APJ. This novel pathway is widely expressed in the cardiovascular system and is emerging as an important mediator of cardiovascular homeostasis. In pre-clinical models, apelin causes venous and arterial vasodilation. METHODS: Vascular effects of apelin were assessed in 24 healthy volunteers. Dorsal hand vein diameter was measured by the Aellig technique during local intravenous infusions (0.1 to 3 nmol/min) of apelin-36, (Pyr(1))apelin-13, and sodium nitroprusside (0.6 nmol/min). Forearm blood flow was measured by venous occlusion plethysmography during intrabrachial infusions of apelin-36 and (Pyr(1))apelin-13 (0.1 to 30 nmol/min) and subsequently in the presence or absence of a "nitric oxide clamp" (nitric oxide synthase inhibitor, L-N(G)-monomethylarginine [8 mumol/min], coinfused with nitric oxide donor, sodium nitroprusside [90 to 900 ng/min]), or a single oral dose of aspirin (600 mg) or matched placebo. RESULTS: Although sodium nitroprusside caused venodilation (p < 0.0001), apelin-36 and (Pyr(1))apelin-13 had no effect on dorsal hand vein diameter (p = 0.2). Both apelin isoforms caused reproducible vasodilation in forearm resistance vessels (p < 0.0001). (Pyr(1))apelin-13-mediated vasodilation was attenuated by the nitric oxide clamp (p = 0.004) but unaffected by aspirin (p = 0.7). CONCLUSIONS: Although having no apparent effect on venous tone, apelin causes nitric oxide-dependent arterial vasodilation in vivo in man. The apelin-APJ system merits further clinical investigation to determine its role in cardiovascular homeostasis.